The main purpose of this proposal is to investigate the occurrence, composition and quantity of circulating antigen-antibody complexes, and other activators and inhibitors of the C system in human cancer. In the human studies, large scale complement assays will represent the primary method of screening large numbers of cancer patients. Those with lower levels or unusual patterns will be studied in special detail. It is expected that the presence of immune complexes will represent a major cause of complement depression but other causes such as inherited defects, presence of C activators and C inhibitors will be sought for. Initial studies have demonstrated strikingly low complement levels in some cancer patients. One of these, a chronic lymphocytic leukemia patient studied in particular detail showed the presence of complexes consisting of antilymphocyte antibody. In addition to detecting and characterizing circular immune complexes, we will attempt to demonstrate whether these complexes relate to specific tumor antigens and antibodies and whether they play a role in the malignant disease. Much of our knowledge of circulating immune complexes, the nature of antigen and antibody, will be derived from the study of animal models, i.e. cats and mice with lymphosarcoma (LSA) or leukemia. Several strains of mice develop glomerulonephritis after infection with murine leukemia virus (MuLV). The disease is associated with the deposition of viral antigens, antibody and complement in the kidneys. LSA in the cat is unique among mammalian cancers in that it is caused by an infectious virus, the feline leukemia virus (FeLV). Most cats, infected with FeLV under natural conditions, remain infected for their entire lives thus raising the possibility that circulating immune complexes exist in these cats. Unpublished work has shown that some viremic cats with LSA have immune complexes in their glomeruli consisting of viral antigen, IgG and Beta 1C. It is thus possible that in infected cats and mice, circulating virus-antibody complexes are trapped in the glomeruli.